Infección por Clostridium difficile: descripción de las cepas NAP1/027 y de otros serotipos en un centro de alta complejidad de Cali, Colombia, 2012-2015 / Clostridium difficile infection: Description of NAP1/027 and non NAP1/027 strains in a high complexity center in Cali, Colombia, 2012-2015

Resumen Introducción. Clostridium difficile ocasiona infecciones hospitalarias que resultan en altas tasas de morbilidad y mortalidad. La cepa NAP1/027 se ha asociado con una mayor producción de toxinas y con una mayor gravedad, lo que aumenta la carga de la enfermedad. Objetivo. Describir la epidemiología de las infecciones asociadas con C. difficile y las características de la cepa NAP1/027. Materiales y métodos. Se hizo un estudio observacional basado en la revisión de las historias clínicas de los pacientes con muestras de heces positivas para C. difficile identificadas mediante la prueba Xpert™ entre el 2012 y el 2015 en un hospital de alta complejidad. La gravedad de la enfermedad se evaluó con el índice ATLAS. Resultados. Se incluyeron 42 casos de pacientes infectados, 9 de los cuales fueron positivos para la cepa NAP1/027. El uso de antibióticos antes de la infección durante más de siete días fue más frecuente en los casos de pacientes con muestras negativas para NAP1/027. En la mitad de los pacientes, la duración de la diarrea fue mayor de cinco días y no hubo diferencias según el tipo de cepa (p>0,05). Los casos de pacientes positivos para la cepa NAP1/027 se caracterizaron por presentar deposiciones fétidas y sanguinolentas. La gravedad de la infección fue similar entre los grupos. Conclusión. Se comprobó la circulación de la cepa NAP1/027, pero su presencia no supuso diferencias clínicas significativas con respecto a otras cepas, lo cual podría deberse al limitado número de pacientes en este estudio. Sin embargo, su presencia debe alertar a los médicos y a las instituciones de salud, dada su frecuente asociación con la gravedad de la infección y la mortalidad.

Abstract Introduction: Clostridium difficile causes nosocomial infections leading to high morbidity and mortality. The NAP1/027 strain is associated with a higher toxin production and disease severity, which increases the load of the disease. Objective: To describe the epidemiology of the infections associated with C. difficile and the characteristics related to the NAP1/027 strain. Materials and methods: This was an observational study based on the revision of clinical registries of patients with fecal samples that were positive for C. difficile identified by the Xpert test™ between 2012 and 2015 in a high complexity institution. The severity of the disease was evaluated by means of the ATLAS score. Results: We included 42 infected cases, 9 of which were positive for the NAP1/027strain. The use of antibiotics previous to the infection for more than seven days was more frequent in patients with negative results for NAP1/027. The duration of diarrhea in half of the patients was longer than five days and there were no differences according to the type of strain (p>0.05). Positive cases for the NAP1/027 strain were characterized by presenting fetid and bloody stools. The severity of the infection was similar between the groups. Conclusions: In Colombia, the NAP1/027 strain circulates without significant clinical differences, which could be due to the limited number of patients. Nevertheless, the existence of NAP1/027 should alert physicians and health institutions because of its high association with severity and mortality.

Colitis pseudomembranosa: a propósito de un caso / Pseudomembranosa colitis: apropos of a case

RESUMEN Fundamento: la colitis pseudomembranosa es una enfermedad causada por el clostridium difficile en los últimos tiempos ha llamado la atención de la comunidad médica, por aumento en la incidencia en las instituciones de salud, así como, en la comunidad, motivado por el consumo frecuente y a veces no ordenado de antimicrobianos. Objetivo: describir un caso de un paciente con diagnóstico postmorten de colitis pseudomembranosa. Caso clínico: paciente masculino de 71 años con antecedentes de enfermedad pulmonar obstructiva crónica y válvula protésica mitral, con esquemas de tratamientos antimicrobianos profilácticos cada mes para evitar infecciones respiratorias, el cual ingresó por presentar deposiciones diarreicas de escasa cantidad pero frecuentes con abundante sangre y moco acompañado de fiebre y dolor abdominal, con una evolución intrahospitalaria tórpida hasta su fallecimiento, el diagnóstico en la necropsia realizada arrojó una colitis pseudomembranosa. Conclusiones: la colitis pseudomembranosa producida por el clostridium difficile es una enfermedad que hay que tener presente en los diagnósticos de paciente hospitalizados los cuales se encuentran con tratamiento antimicrobianos o que procedan de la comunidad donde se les prescribió con este tipo de fármacos.

ABSTRACT Background: pseudomembranous colitis is a disease caused by Clostridium difficile in recent times has attracted the attention of the medical community, due to an increase in the incidence in health institutions, as well as in the community, motivated by the more frequent use and sometimes not ordered antimicrobials. Objective: to describe a case of a patient with a postmortem diagnosis of pseudomembranous colitis. Clinical case: a 71-year-old male patient with a history of chronic obstructive pulmonary disease and mitral prosthetic valve to receive from several months prophylactic antimicrobial cycles every month to avoid respiratory infections, who is admitted due to scarce diarrheic stools, but frequent with abundant blood and mucus accompanied by fever and abdominal pain, with an intra-hospital torpid evolution until his death, performing the diagnosis of pseudomembranous colitis in the necropsy study. Conclusions: the pseudomembranous colitis produced by Clostridium difficile is a disease that has to be kept in mind in the diagnoses of hospitalized patients who are under antimicrobial treatment or who come from the community where they were prescribed with this type of drugs.

Fecal microbiota transplantation in the treatment of Clostridium difficile infection: state of the art and literature review / Transplante de microbiota fecal no tratamento da infecção por Clostridium difficile: estado da arte e revisão de literatura

ABSTRACT Clostridium difficile infection is a common complication following intestinal dysbiosis caused by abusive antibiotic use. It presents medical importance due to the high rates of recurrence and morbidity. Fecal microbiota transplantation is an effective alternative for the treatment of recurrent and refractory C. difficile infection and consists of introducing the intestinal microbiota from a healthy donor into a patient with this infection. The exact physiological mechanism by which fecal microbiota transplantation alters the intestinal microbiota is not well established, but it is clear that it restores the diversity and structure of the microbiota by promoting increased resistance to colonization by C. difficile. Several routes of transplant administration are being studied and used according to the advantages presented. All forms of application had a high cure rate, and the colonoscopic route was the most used. No relevant complications and adverse events have been documented, and the cost-effectiveness over conventional treatment has proven advantageous. Despite its efficacy, it is not commonly used as initial therapy, and more studies are needed to establish this therapy as the first option in case of refractory and recurrent Clostridium difficileinfection.

RESUMO A infecção por Clostridium difficile é uma complicação comum após a disbiose intestinal ocasionada pelo uso abusivo de antibióticos. Apresenta elevada importância médica devido às altas taxas de recorrência e morbidade. O transplante de microbiota fecal é uma alternativa eficaz para o tratamento da infecção recorrente e refratária pelo C. difficile e consiste na introdução da microbiota intestinal de um doador saudável em um paciente portador desta infecção. O mecanismo fisiológico exato pelo qual o transplante de microbiota fecal altera a microbiota intestinal não está tão bem estabelecido, mas é evidente que restaura a diversidade e a estrutura da microbiota promovendo aumento da resistência à colonização pelo C.difficile. Diversas vias de administração do transplante estão sendo estudadas e utilizadas de acordo com as vantagens apresentadas. Todas as formas de aplicação apresentaram elevada taxa de cura, sendo a via colonoscópica a mais utilizada. Não foram documentados complicações e efeitos adversos relevantes, e seu custo benefício em relação ao tratamento convencional se mostrou vantajoso. Apesar da sua eficácia é pouco utilizado como terapia inicial, sendo necessários mais estudos para firmar essa terapêutica como primeira opção no caso de infecção por Clostridium difficile refratária e recorrente.

Características de la infección por Clostridium difficile en una institución de alta complejidad y reporte de la circulación en Colombia de la cepa hipervirulenta NAP1/027 / Characteristics of Clostridium difficile infection in a high complexity hospital and report of the circulation of the NAP1/027 hypervirulent strain in Colombia

Resumen Introducción. Clostridium difficile es el principal responsable de la diarrea asociada al uso de antibióticos. En Colombia y en Latinoamérica, el conocimiento sobre el comportamiento epidemiológico de la infección por C. difficile todavía es limitado. Objetivo. Describir las características de una serie de pacientes con infección por C.difficile . Materiales y métodos. Se hizo un estudio descriptivo de una serie de casos de pacientes con infección por C. difficile atendidos en la Fundación Clínica Shaio, entre enero de 2012 y noviembre de 2015. Resultados. Se estudiaron 36 pacientes con una edad promedio de 65 años. Se determinaron los siguientes factores relacionados con la infección por C. difficile: uso previo de antimicrobianos (94,4 %), hospitalización en los últimos tres meses (66,7 %) y uso de inhibidores de la bomba de protones (50 %). Las comorbilidades más comunes fueron la enfermedad renal crónica (41,7 %) y la diabetes mellitus (30,6 %). Los síntomas más frecuentes fueron más de tres deposiciones diarreicas (97,1 %) y dolor abdominal (42,9 %). En cuanto a la gravedad de los casos, 44,4 % se clasificó como leve a moderado, 38,9 % como grave, y 11,1 % como complicado o grave. El método de diagnóstico más utilizado (63,8% de los pacientes) fue la identificación de la toxina mediante reacción en cadena de la polimerasa (PCR). La mortalidad global durante la hospitalización fue de 8 %. Se identificaron cuatro cepas del serotipo NAP1/027 y nueve muestras fueron positivas para la toxina binaria. Conclusión. La infección por C. difficile debe sospecharse en pacientes con deposiciones diarreicas y factores asociados tradicionalmente a esta enfermedad. Se reportó la circulación de cepas hipervirulentas del serotipo NAP1/027 en Colombia, lo cual debe enfrentarse con la vigilancia epidemiológica y el diagnóstico temprano.

Abstract Introduction: Clostridium difficile is the main pathogen related to healthcare-associated diarrhea and it is the cause of 20 to 30% of diarrhea cases caused by antibiotics. In Colombia and Latin America, the knowledge about the epidemiological behavior of this infection is limited. Objective: To describe the characteristics of a series of patients with C. difficile infection. Materials and methods: We performed a descriptive case series study of patients with C. difficile infection hospitalized in the Fundación Clínica Shaio from January, 2012, to November, 2015. Results: We analyzed 36 patients. The average age was 65 years. The risk factors associated with the infection were: previous use of antibiotics (94.4%), prior hospitalization in the last three months (66.7%) and use of proton pump inhibitors (50%). The most common comorbidities were chronic kidney disease (41.7%) and diabetes mellitus (30.6%). The most frequent symptoms were more than three loose stools per day (97.1%) and abdominal pain (42.9%). According to the severity of the disease, 44.4% of cases were classified as mild to moderate, 38.9% as severe, and 11.1% as complicated or severe. The detection of the toxin by PCR (GeneXpert) was the most common diagnostic procedure (63.8%). Global mortality during hospitalization was 8%. We identified four strains with serotype NAP1/027 and nine samples positive for binary toxin. Conclusion: Clostridium difficile infection should be suspected in patients with diarrhea and traditional risk factors associated with this disease. We report the circulation of the hypervirulent strain serotype NAP1/027 in Colombia, which should be countered with epidemiological surveillance and a prompt diagnosis.

Colitis seudomembranosa como hallazgo posmortemen paciente pediátrico. Reporte de caso / Pseudomembranous colitis as postmortem finding in pediatric patient. Case report

La colitis seudomembranosa es una severa y a veces mortal afección que puede ocurrir tras la administración de antibióticos y supresión de la flora intestinal normal, seguida de colonización por Clostridium difficile; se caracteriza por la inflamación aguda y presencia de seudomembranas necróticas en la mucosa colónica. Se presenta el caso de un paciente varón de nueve años de edad, proveniente de una zona rural de Honduras, con antecedente de fiebre intermitente de cuatro semanas de evolución, escalofríos, mialgias, náuseas e ictericia de una semana de evolución. Atendido previamente en Centro de Atención Primaria, fue tratado con antipiréticos, sin mejoría. Al examen físico el paciente estaba lúcido, se halló hipotensión, taquicardia, y fiebre; dolor abdominal epigastrio y ambos hipocondrios a la palpación superficial y profunda, hepatomegalia, ictericia, petequias. En los exámenes de laboratorio se encontraron pancitopenia severa, falla renal aguda, trastornos hidroelectrolíticos e hipoalbuminemia. Fue ingresado al servicio de urgencias pediátricas. Luego de una mala evolución clínica, falleció diecinueve después del ingreso. La autopsia reveló seudomembranas necróticas colónicas e imagen histológica de tipo volcán compatibles con colitis seudomembranosa.

Pseudomembranous colitis is a severe and often fatal condition that may occur after the administration of some antimicrobial agents. There is suppression of the normal intestinal flora, followed by colonization by Clostridium difficile; and this condition is characterized by acute inflammation and presence of necrotic tissue pseudomembranes in the colon mucosa. We present the case of a nine-year-old boy from a rural area in Honduras, with a history of intermittent fever lasting four weeks, accompanied by chills, myalgia, nausea, and jaundice in the last week. He was previously seen in a primary care center with antipyretics, without improvement. The physical examination showed a lucid patient with hypotension, tachycardia, and fever; epigastric and bilateral hypochondrial abdominal pain on superficial and deep palpation was evidenced. Hepatomegaly, jaundice, and petechiae were also found. Laboratory tests showed severe pancytopenia, acute renal failure, hydroelectrolytic disturbances, and hypoalbuminemia. The patient was admitted to the Pediatric Urgency service. After a poor progression, he passed away nineteen days after admission. The necropsy showed necrotic pseudomembranes in the colon and a histological image resembling the shape of a volcano, compatible with pseudomembranous colitis.

Refractory pseudomembranous colitis that was treated successfully with colonoscopic fecal microbial transplantation

Pseudomembranous colitis (PMC) is a nosocomial and opportunistic infection caused by Clostridium difficile. PMC is related to the use of antibiotics leading to intestinal dysbiosis and an overgrowth of C. difficile. Metronidazole or vancomycin is considered to be the standard therapy for the management of PMC. However, PMC has a 15%-30% recurrence rate and can be refractory to standard treatments, resulting in morbidity and mortality. Here we describe a patient who experienced refractory PMC who was treated with fecal microbiota transplantation. A 69-year-old woman was admitted to the hospital with consistent abdominal pain and diarrhea, which had been present for 5 months. She was diagnosed with PMC by colonoscopy and tested positive for C. difficile toxin. Even though she took metronidazole for 10 days, followed by vancomycin for 4 weeks, her symptoms did not improve. Because of her recurrent and refractory symptoms, we decided to perform fecal microbiota transplantation. Fifty grams of fresh feces from a donor were obtained on the day of the procedure, mixed with 500 mL of normal saline, and then filtered. The filtered solution was administered to the patient's colon using a colonoscope. After the procedure, her symptoms rapidly improved and a follow-up colonoscopy showed that the PMC had resolved without recurrence.

Refractory Clostridium difficile Infection Cured With Fecal Microbiota Transplantation in Vancomycin-Resistant Enterococcus Colonized Patient

The rates and severity of Clostridium difficile infections, including pseudomembranous colitis, have increased markedly. However, there are few effective treatments for refractory or recurrent C. difficile infections and the outcomes are poor. Fecal microbiota transplantation is becoming increasingly accepted as an effective and safe intervention in patients with recurrent disease, likely due to the restoration of a disrupted microbiome. Cure rates of >90% are being consistently reported from multiple centers. We cured a case of severe refractory C. difficile infection with fecal microbiota transplantation in a patient colonized by vancomycin-resistant enterococcus.

The Simple Predictors of Pseudomembranous Colitis in Patients with Hospital-Acquired Diarrhea: A Prospective Observational Study

BACKGROUND/AIMS: As the incidence rate of and mortality from pseudomembranous colitis (PMC) are increasing worldwide, it is important to study the simple predictive risk factors for PMC among patients with hospital-acquired diarrhea (HAD). This study focused on identifying the clinical risk factors that can easily predict PMC. METHODS: The presumed HAD patients were prospectively recruited at the Hallym University Kangdong Sacred Heart Hospital. RESULTS: Age of 70 and older (adjusted odds ratio [OR], 1.76; 95% confidence interval [CI], 1.12 to 0.75), use of proton pump inhibitors (adjusted OR, 4.07; 95% CI, 2.512 to 6.57), use of cephalosporins (adjusted OR, 2.99; 95% CI, 1.82 to 4.94), and underlying cancer (adjusted OR, 1.72; 95% CI, 1.04 to 2.82) were independent risk factors for PMC in the multivariate logistic regression analysis. The prevalence of PMC was very low in the patients with HAD who exhibited no risk factors. CONCLUSIONS: The risk factors for PMC in patients with HAD included cephalosporin use, proton pump inhibitor use, old age, and cancer. Considering the strongly negative predictive values of these risk factors, endoscopic evaluation can be delayed in patients with HAD without risk of developing PMC.

Progress of laboratory diagnostic methods of Clostridium difficile infection / 中华检验医学杂志

Clostridium difficile is a gram-positive,anaerobic spore-forming bacillus commonly found in the environment and human gut.Excessive use of antibiotics,immunosuppressive agents and chemotherapy drugs may lead to overgrowth of the toxic strain of Clostridium difficile with high resistance,which are supposed to be the major contributing factors leading to Clostridium difficile associated diarrhea(CDAD).The globally increasing incidence of CDAD,especially the outbreak of nosocomial infection caused by the hypervirulent strain in North America,arouse worldwide attention.For providing new ideas to the early diagnosis and treatment of CDAD,this review summarize the latest development on pathogenesis and rapid laboratory diagnosis of Clostridium difficile.

Ulcerative Colitis Complicating Pseudomembranous Colitis of the Right Colon

Clostridium difficile (C. difficile) is a cytotoxin-producing anaerobic gram-positive rod that is responsible for pseudomembranous colitis (PMC). The incidence of C. difficile is increasing in ulcerative colitis (UC) and inflammatory bowel disease patients and is associated with a more severe course, a longer hospital stay, higher financial costs, a greater likelihood of colectomy, and high mortality. PMC may occur anywhere along the intestinal tract, but it is often found in the distal colon. PMC involving the proximal colon with rectosigmoid sparing is rarely reported in patients with UC. We describe the case of a 35-year-old woman in remission from UC who presented with frequent diarrhea and abdominal pain. She was treated with ciprofloxacin for infectious enterocolitis at a local hospital; however, her symptoms did not improve. A colonoscopy revealed yellow-white plaques with edematous, erythematous from the proximal ascending colon to the cecum, and feces positive for C. difficile toxin. She was treated with metronidazole (500 mg, three times a day) for two weeks, and improved rapidly. Physicians should carefully examine the entire colon via colonoscopy, and perform stool exams for C. difficile in patients with UC who have been treated with antibiotics and in those who develop prolonged diarrhea despite medical treatment.

Rifampin-induced Pseudomembranous Colitis with Rectosigmoid Sparing

Pseudomembranous colitis (PMC) is known to be associated with antibiotic treatment, but is not commonly related to antitubercular (anti-TB) agent, rifampin. PMC is frequently localized to rectum and sigmoid colon, which can be diagnosed with sigmoidoscopy. We report a case of rifampin-induced PMC with rectosigmoid sparing in a pulmonary tuberculosis patient. An 81-year-old man using anti-TB agents was admitted with a 30-day history of severe diarrhea and general weakness. On colonoscopy, nonspecific findings such as mucosal edema and erosion were found in sigmoid colon, whereas multiple yellowish plaques were confined to cecal mucosa only. Biopsy specimen of the cecum was compatible with PMC. Metronidazole was started orally, and the anti-TB medications excluding rifampin were readministerred. His symptoms remarkably improved within a few days without recurrence. Awareness of rectosigmoid sparing PMC in patients who develop diarrhea during anti-TB treatment should encourage early total colonoscopy.

The First Case of Antibiotic-associated Colitis by Clostridium difficile PCR Ribotype 027 in Korea

Clostridium difficile (C. difficile) is a common causative agent of pseudomembranous colitis (PMC). C. difficile-associated diarrhea (CDAD) ranges from mild diarrhea to life threatening PMC. Recently, a highly virulent strain of C. difficile polymerase chain reaction ribotype 027 was found in North America, Europe, and Japan. A 52-yr-old woman with anti-tuberculosis medication and neurogenic bladder due to traffic accident experienced five episodes of C. difficile PMC after taking antibiotics for pneumonia along with septic shock and acute renal failure. She was readmitted to the intensive care unit and treated with oral vancomycin with refractory of oral metronidazole, inotropics and probiotics for over 60 days. C. difficile isolated both at the first and the last admission was identified as C. difficile ribotype 027 by ribotyping, toxinotyping, and tcdC gene sequencing, which turned out the same pathogen as the epidemic hypervirulent B1/NAP1 strain. This is the first case of C. difficile PCR ribotype 027 in Korea. After discharge, she was maintained on probiotics and rifaximin for 3 weeks. She had no relapse for 6 months.